The overall objective of this project is to investigate the employment of the reticuloendothelial stimulant, glucan, as an agent for the initiation of macrophage induced destruction of malignant cells. The intralesional injection of glucan has been demonstrated in our rather extensive preliminary clinical investigations, to be effective in inducing macrophage mediated destruction of three types of malignant lesions in man. It is proposed to expand this investigation in experimental animals relative to the possibility of using glucan systemically in order to produce generalized macrophage activation in an effort to affect disseminated tumors. The mechanisms of the macrophage mediated antitumor action of glucan will be investigated by assessment of metabolic, functional and ultrastructural alterations induced in macrophages as well as in tumor cells, both in vivo and in vitro. The role of recognition factors, which are essential for the discriminative action of macrophages, will also be studied in neoplasia. The ability of this opsonic fraction to complex with tumor cells and thereby enhance recognition of these cells by macrophages will be investigated in in vitro and in vivo systems. Our studies will evaluate our concept that macrophages, in their role as both monitor and killer cells, are essential in maintaining the internal environment free of malignant cells. These studies will also contribute to the potential clinical development of useful macrophage activating agents which can be utilized in enhancing host mediated tumor cell destruction.